POLR2J2 encodes the RPB11 subunit of RNA polymerase II, a core component of the basal transcription machinery responsible for synthesizing mRNA precursors and functional non-coding RNAs 1. As part of the mobile elements within Pol II's central cleft, POLR2J2 contributes to the DNA-dependent RNA polymerase activity essential for transcription by RNA polymerase II. POLR2J2 is one of four human POLR2J family members located on chromosome 7, with alternative splicing generating at least 14 distinct RPB11 isoforms 1. Disease relevance includes Huntington's disease, where miR-34a-5p directly targets POLR2J2, suggesting dysregulation of transcriptional machinery may contribute to pathogenesis 2. POLR2J2 also exhibits race-specific transcriptional differences in colon cancer patients, representing part of a five-gene signature associated with disparities between Black and white patients across all disease stages 3. Additionally, POLR2J2 was identified in copy number variations in thyroid-like nasopharyngeal papillary adenocarcinoma 4. These findings indicate POLR2J2 dysfunction may contribute to both neurodegenerative and neoplastic disease pathogenesis through alterations in transcriptional regulation.